Helferich synthesis

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The Helferich synthesis , also Helferich and Schmitz-Hillebrecht synthesis , is a name reaction in organic chemistry. It was first discovered in 1933 by the German chemist Burckhardt Helferich (1887–1982) and the chemist E. Schmitz-Hillebrecht . It is used for the direct synthesis of phenyl glycoside from monosaccharide pentaacetate and phenol with acid catalysis.

Overview reaction

In this reaction, a five-fold acetylated carbohydrate ring reacts with phenol in an acidic environment to form acetylated phenyl glycoside. In the presence of ZnCl 2 , the α-glycoside is formed with the phenoxy radical in the axial position. When adding p -toluenesulfonic acid (TsOH), however, the β-glycoside is formed with the phenoxy radical in the equatorial position.

Helferich synthesis - overview reaction

Reaction mechanism

Zinc chloride catalyst - α-glycoside formation

In the proposed reaction mechanism, an α-phenyl glycoside 3 is formed :

Helferich synthesis - reaction mechanism

It is assumed that the oxygen atom in the carbohydrate ring and that of the carbonyl group of 1 initially interact with the ZnCl 2 . The phenol is then added to 2 . In a transition state, the phenol attacks from the underside and the formation of the α-phenyl glycoside 3 occurs .

Catalyst p -toluenesulfonic acid - β-glycoside formation

The β-phenyl glycoside 3 is formed - according to Zerong Wang - along the following reaction chain:

Helferich synthesis - reaction mechanism

When TsOH acts on 1 , acetic acid (AcOH) is first split off, thus forming the oxonium ion 2 . When phenol is added, the tosylate anion first abstracts a proton, forming a phenoxy anion, which immediately attacks 2 , with the β-glycoside 3 being formed diastereoselectively .

See also

Individual evidence

  1. ^ Winfried R. Pötsch, Annelore Fischer, Wolfgang Müller with the assistance of Heinz Cassebaum: Lexicon of important chemists . Bibliographisches Institut, Leipzig 1988, p. 384, ISBN 3-323-00185-0 .
  2. ↑ Eberhard Breitmaier, Günther Jung: Organic Chemistry: Fundamentals, Compound Classes, Reactions, Concepts, Molecular Structure, Natural Products, Synthesis Planning, Sustainability Vol. 7. Georg Thieme Verlag, Stuttgart, 2012, pp. 872–873, ISBN 978-3-13- 541507-9 .
  3. ↑ a b c d e Zerong Wang: Comprehensive Organic Name Reactions and Reagents , Wiley, 2010, ISBN 9780470638859 , pp. 1363-1366, doi: 10.1002 / 9780470638859 .
  4. ↑ Martha Windholz, Susan Budavari, Lorraine Y. Stroumtos, Margaret Noether Done: The Merck Index An Encyclopedia of Chemicals and Drugs Vol. 9, Merck & Co., INC., Rahway, NJ, 1976, ISBN 0-911910-26- 3 , p. ONR-41.